The proposed research project is designed to identify and determine the clinical role of genetic determinants of host susceptibility to anemia with falciparum malaria in Thailand. Malaria provides the paradigm for a disease that has shaped the human genome through natural selection of protective genetic traits. More genes have now been implicated in variability of susceptibility to malaria than to any other infectious or non- infectious disease of humans. Genes now recognized as affecting the host response to malaria include those for hemoglobin variants, for red blood cell enzymes, components of the membrane cytoskeleton, membrane receptors and blood group proteins, as well as loci that modulate immune responses or are involved in underlying pathophysiologic processes. The proposed research will seek to identify and characterize the clinical consequences of genetic determinants of a specific complication of malaria infection-anemia-in three prospective trials, designed to detect a variety of types of protection against falciparum malarial infection- anemia-in three prospective trials, designed to detect a variety of types of protection against falciparum malaria in population-based, case-control and hospital-based studies. Project 1 has three specific aims: (1) to conduct a prospective, population-based study of the hemoglobin levels and genotypes of children and adults with malarial infection as detected by monthly mass blood survey and permanent passive case detection at a field site in western Thailand (Suan Phung); (2) to conduct a prospective, case-control study of the genotypes of children and adults who present with symptomatic episodes of falciparum malaria at another field site in western Thailand (Bongti); and (3) to conduct a prospective, hospital-based study of the genotypes of children and adults with severe anemia in falciparum malaria who are admitted to the Hospital for Tropical Disease, Bangkok. DNA from all participants will be stored in a repository. The special characteristics of Thai populations may facilitate the identification of a variety of unrecognized genetic forms of "innate", non-immune modes of host resistance, and lead to new prevention and treatment strategies.